High-fat diet in utero protects against Alzheimer's later
August 27, 2019
Science Daily/Temple University Health System
A high-fat diet can carry health risks, but for mothers-to-be, it may make all the difference when it comes to Alzheimer's disease prevention for their children. In a report published online August 26 in the journal Molecular Psychiatry, researchers at the Lewis Katz School of Medicine at Temple University show for the first time in animals that high maternal fat consumption during gestation protects offspring against changes in the brain that are characteristic of late-onset Alzheimer's disease.
"In humans, it has been known that individuals whose mothers develop Alzheimer's disease after age 65 are at increased risk of also developing the disease around the same age," said senior investigator Domenico Praticò, MD, Scott Richards North Star Foundation Chair for Alzheimer's Research, Professor in the Departments of Pharmacology and Microbiology, and Director of the Alzheimer's Center at Temple at the Lewis Katz School of Medicine.
Genetic factors transmitted by mothers to their offspring seem like an obvious explanation behind this phenomenon, but so far no genes have been identified that could explain the maternal transmission of Alzheimer's disease. This fact would suggest that environmental factors, such as lifestyle and diet, adopted during the gestation period, a time in which mother and baby are in tight interaction, could significantly influence the offspring's risk of developing the disease later in life.
Diet is of particular interest as a risk factor, especially a diet rich in animal fat and cholesterol. High-fat intake previously has been shown in young/adult mice to directly exacerbate the types of changes in brain function that ultimately may contribute to Alzheimer's disease.
To better understand the unique relationship between maternal Alzheimer's disease and risk in her offspring, Dr. Praticò and colleagues looked at maternal fat intake specifically during the gestation period in mice engineered to develop Alzheimer's disease. Pregnant mice were fed a high-fat diet from the beginning until the end of gestation. The moment offspring were born, mothers were switched to a regular diet, which was maintained during the lactation period. Offspring of these mothers were always kept at the same regular, or standard, diet throughout their life.
At 11 months of age, offspring underwent behavioral tests to assess learning ability and memory. "Surprisingly, we found that animals from mothers fed a high-fat diet during gestation had better learning and memory skills than their counterparts born to mothers fed a regular diet during gestation," Dr. Praticò said.
The observed improvements in memory and learning were associated with the maintenance of good synaptic integrity. In fact, offspring from mothers exposed to a high-fat diet had significant improvement of synapse function when compared with offspring from mothers on a regular diet. Synapses, the places where neurons come together to relay information, play a vital role in learning and memory formation.
In addition, compared to animals born to mothers fed a regular diet, offspring from mothers on a high-fat diet had lower levels of amyloid-beta, an abnormal protein that builds up in neurons, contributing to nerve cell dysfunction and eventually significant impairments in memory and learning
When the team searched for possible mechanisms responsible for the beneficial effect, they discovered that offspring from mothers fed a high-fat diet exhibited reduced levels of three important genes involved in Alzheimer's disease: beta-secretase, tau, and the pathological tau-regulating gene CDK5. Dr. Praticò's team found that already in the early developmental stages, the three genes were effectively switched off in offspring because the high-fat diet had increased activity of a protein called FOXP2. They demonstrated that the repressive activity of FOXP2 on these genes ultimately protected offspring from later declines in brain function and Alzheimer's disease development.
"Our findings suggest that, to be effective, Alzheimer's disease prevention probably needs to start very early in life, during gestation," Dr. Praticò said. "Diet at this specific life stage can have critical, but underestimated, long-term impacts on brain health."
Dr. Praticò and colleagues plan next to compare the effects of a high-fat diet to those of other diets, including diets high in sugar and protein and diets resembling the Mediterranean diet in humans. "We also want to see whether our findings can be replicated in wild-type animals" Dr. Praticò added.
https://www.sciencedaily.com/releases/2019/08/190827084717.htm
Effects of a high-fat diet may be passed on for three generations
October 12, 2018
Science Daily/BioMed Central
A high-fat diet in female mice affects their offspring's obesity, insulin resistance and addictive-like behaviors for three generations, according to a new study.
Researchers at ETH Zurich, Switzerland showed that second generation offspring -- grandchildren of mice that had consumed a high-fat diet before, during and after pregnancy showed addictive-like behaviors such as increased sensitivity and preference for drugs, as well as characteristics of obesity, including changes in their metabolism. In third generation offspring (the great grandchildren), the authors observed differences between males and females, with only females showing addictive-like behaviors and only males showing obesity characteristics.
This was the case although the original female mice themselves never became obese and although none of the following generations consumed a high-fat diet.
Dr Daria Peleg-Raibstein, the corresponding author said: "Most studies so far have only looked at the second generation or followed the long-term effects of obesity and diabetes on the immediate offspring. This study is the first to look at the effects of maternal overeating up until the third generation in the context of addiction as well as obesity."
The authors investigated these effects specifically for transmission via male offspring up until, and including, the third generation. To do so, they fed female mice either high-fat diet or a standard laboratory diet for nine weeks -- pre-mating, during pregnancy and during lactation. Their male offspring were then mated with females that had been fed a standard laboratory diet to generate the second-generation offspring. The male offspring of these mice was again mated with females that had been fed a standard laboratory diet to generate the third-generation offspring.
The authors measured body weight, insulin sensitivity, metabolic rates, and blood plasma parameters such as insulin and cholesterol in second and third-generation offspring. In behavioral experiments they investigated if the mice chose a high-fat over a standard laboratory diet or an alcohol solution over water, as well as their activity levels after exposure to amphetamines. They did this to better understand if a maternal high-fat diet had an effect on obesity, overeating and drug sensitivity in subsequent generations.
Dr Peleg-Raibstein said: "To combat the current obesity epidemic, it is important to identify the underlying mechanisms and to find ways for early prevention. The research could help improve health advice and education for pregnant and breastfeeding couples and give their children, grandchildren and great-grandchildren a better chance of a healthy lifestyle. It may also provide a way of identifying risk factors for how people develop obesity and addiction and suggest early interventions for at-risk groups."
Dr Peleg-Raibstein added: "It is quite a leap to apply conclusions from mouse studies to humans, but studying effects of maternal over-eating is almost impossible to do in people because there are so many confounding factors, such as socio-economic background, the parents' food preferences or their existing health conditions. The mouse model allowed us to study the effects of a high-fat diet on subsequent generations without these factors."
Further studies are needed to determine the molecular mechanism by which the effects of a female high-fat diet may be passed on to following generations.
https://www.sciencedaily.com/releases/2018/10/181012082710.htm